tbuckley/cabot-search huggingface dataset:
Abstract P3-07-20: Treatment of 4T1 Breast Cancer with Liposome-Encapsulated AdAPT-001, a TGF-beta Trap Encoded Oncolytic Adenovirus Currently in a Phase 1/2 Anticancer Trial
Authors: Tony Reid, Andrew Kummel, Scott Caroen, Jaimin Shah, Bryan Oronsky, Christopher Larson
Journal: Cancer Research (2023)

Abstract Adenoviral vectors have been used extensively for gene therapy. However, efficient infection of cells requires expression of the coxsackie-adenoviral receptor (CAR). Many tumor cells lack adequate expression of CAR and, hence, are not good targets for adenoviral based vectors. We have developed a unique nanoparticle (Epi-039) that can be used to efficiently introduce adenoviral vectors into tumor cells that have low or no CAR expression. We used the CAR-negative 4T1 mammary carcinoma model system, which represents a typical triple-negative breast cancer cell line (ER−, PR−, HER2−) and which is refractory to adenoviral infection to demonstrate effective transduction of an encapsulated oncolytic adenovirus. The adenovirus that was used is called AdAPT-001. This armed oncolytic virus, which is currently in a phase I/II clinical trial called BETA PRIME for the treatment of refractory cancers, expresses a TGFb receptor trap to neutralize the immunosuppressive cytokine, TGF beta. Overexpression of TGF-beta positively correlates with metastasis in breast carcinoma and thus confers a poorer prognosis. In this study, the unique Epi-039 nanoparticle carrying AdAPT-001 not only significantly enhanced the transduction efficiency of AdAPT-001 but also protected it from neutralization by natural antibodies in human whole blood. Accordingly, we demonstrate a significant increase (P value= 0.0029) in the expression of green fluorescent protein (GFP) in CAR-negative 4T1 cells infected with the encapsulated AdAPT-001 adenovirus but not the unencapsulated AdAPT-001 adenovirus. Additional in vivo studies using nanoparticle encapsulated adenoviral vectors including AdAPT-001 to treat breast cancer are underway for rapid translation to the clinic. Citation Format: Tony Reid, Andrew Kummel, Scott Caroen, Jaimin Shah, Bryan Oronsky, Christopher Larson. Treatment of 4T1 Breast Cancer with Liposome-Encapsulated AdAPT-001, a TGF-beta Trap Encoded Oncolytic Adenovirus Currently in a Phase 1/2 Anticancer Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-20.
Abstract P4-03-37: The characteristics of male breast cancer by molecular subtypes: a population-based study
Authors: Min Wang, Deyue Liu, Li Zhu
Journal: Cancer Research (2023)

Abstract Background: To explore the characteristics of molecular subtype in male breast cancer. Methods: A retrospective study was conducted to investigate the characteristics and prognosis of patients with male breast cancer using the data recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010-2014. Results: A total of 1597 cases were enrolled, including 1373 cases with HR+/HER2- (86%), 182 cases with HR+/HER+ (11.4%), 13 cases with HR-/HER2+ (0.8%) and 29 cases with Triple Negative (1.8%), respectively. There were significant differences in distributions in age, race, grade, tumor size and AJCC stage between the molecular subtypes. The molecular subtypes differed significantly in 5 years overall survival and 5 years cause specific survival, establishing the following sequence with HER2-/HR+ &amp;gt; HER2+/HR+ &amp;gt; HER2+/HR- &amp;gt; Triple negative. According to Cox regression, age&amp;gt;65y, ER negative, PR negative, TN subtype, advanced AJCC stage, larger tumor size, stage T3 and M1 were independent prognostic factors for poorer survival. Conclusion: The prognosis of male breast cancer varied by molecular subtypes. Age, ER and PR, status, stage as well as tumor size were independent prognostic factors. Citation Format: Min Wang, Deyue Liu, Li Zhu. The characteristics of male breast cancer by molecular subtypes: a population-based study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-37.
Abstract P4-08-09: Deoxycytidine kinase (dCK) inhibition is synthetic lethal with BRCA2-deficiency
Authors: María L. Guantay, Cintia A. Garro, Sebastian Siri, María Pansa, Sonja Ghidelli-Disse, Natalia Paviolo, Ana Racca, Viviana Nicotra, Caius Radu, José L. Bocco, Rosana Felice, Israel Gloger, Marcel Muelbaier, Gerard Drewes, Kevin Madauss, Manuela García, Vanesa Gottifredi, Gastón Soria
Journal: Cancer Research (2023)

Abstract BRCA2 is a well-established cancer driver in several human malignancies. While the remarkable success of PARP inhibitors proved the clinical potential of targeting BRCA deficiencies, the emergence of resistance mechanisms underscores the importance of seeking novel Synthetic Lethal (SL) targets for future drug development efforts. In this work, we performed a BRCA2-centric SL screen with a collection of plant-derived compounds from South America. We identified the steroidal alkaloid Solanocapsine as a selective SL inducer, and we were able to substantially increase its potency by deriving multiple analogs. The use of two complementary chemoproteomic approaches led to the identification of the nucleotide salvage pathway enzyme deoxycytidine kinase (dCK) as Solanocapsine’s target responsible for its BRCA2-liked SL induction. Additional confirmatory evidence was obtained by using a highly specific dCK inhibitor (DI-87), which induces SL in multiple BRCA2-deficient and KO contexts. Interestingly, dCK-induced SL is mechanistically different from the one induced by PARP inhibitors. dCK inhibition generates substantially lower levels of DNA damage, and cytotoxic phenotypes are associated exclusively with mitosis, thus suggesting that the fine-tuning of nucleotide supply in mitosis is critical for the survival of BRCA2-deficient cells. Moreover, by using a xenograft model of contralateral tumors, we show that dCK impairment suffices to trigger SL in-vivo. Taken together, our findings unveil dCK as a promising new target for BRCA2-deficient cancers, which provides future therapeutic alternatives to PARP inhibitors. Citation Format: María L. Guantay, Cintia A. Garro, Sebastian Siri, María Pansa, Sonja Ghidelli-Disse, Natalia Paviolo, Ana Racca, Viviana Nicotra, Caius Radu, José L. Bocco, Rosana Felice, Israel Gloger, Marcel Muelbaier, Gerard Drewes, Kevin Madauss, Manuela García, Vanesa Gottifredi, Gastón Soria. Deoxycytidine kinase (dCK) inhibition is synthetic lethal with BRCA2-deficiency [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-09.
Abstract P2-15-09: Impact of neoadjuvant chemotherapy on the short- and long-term outcomes in patients who underwent immediate breast reconstruction after mastectomy
Authors: Hiroko Nogi, Akiko ogiya, Naoto Kondo, Makoto Ishitobi, Chikako Yamauchi, Hiroki Mori, Ayaka Shimo, Kazutaka Narui, Naomi Nagura, Hirohito Seki, Shinsuke Sasada, Teruhisa Sakurai, Tadahiko Shien
Journal: Cancer Research (2023)

Abstract Background and Purpose In breast cancer patients receiving neoadjuvant chemotherapy (NAC), the use of immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. The Japanese breast cancer society conducted retrospective multicenter cohort study in the era of IBR, and we assessed the impact of NAC on surgical and oncological outcomes in patients underwent IBR. Methods Between January 2008 and December 2016, 473 (10.0%) breast cancer cases received NAC of 4726 cases underwent IBR after mastectomy. The clinicopathological and survival data of patients who received NAC (the NAC group) and those who did not receive NAC (the control group) were compared in terms of postoperative complications (infection, hemorrhage, seroma, dehiscence, tissue expander or implant loss, flap or skin necrosis) and oncologic safety. Results Eight-hundred forty cases had minor or major complications. NAC did not increase the risk of complications after IBR (OR 1.20; 95%CI 0.95 - 1.53; p = 0.13). Smoking (OR 1.35; 95%CI 1.14 - 1.62; p = 0.001), overweight (BMI25≤) (OR 1.94; 95%CI 1.61 - 2.35; p &amp;lt; 0.001), PMRT (OR 1.54; 95%CI 1.20 - 1.99; p = 0.01) increased risk of complications. At the median follow-up time of 76.5 months, 36 patient (7.6%) in the NAC group and 147 patients (3.5%) in the control group had local recurrence. 35 patient (7.4%) in the NAC group and 147 patients (2.0%) in the control group had reginal recurrence. Conclusion Immediate breast reconstruction after NAC is a safe procedure with post-operative complication profile. It can be performed safely and therefore should be considered as a strategy preferred for patients with local advanced breast cancer. Citation Format: Hiroko Nogi, Akiko ogiya, Naoto Kondo, Makoto Ishitobi, Chikako Yamauchi, Hiroki Mori, Ayaka Shimo, Kazutaka Narui, Naomi Nagura, Hirohito Seki, Shinsuke Sasada, Teruhisa Sakurai, Tadahiko Shien. Impact of neoadjuvant chemotherapy on the short- and long-term outcomes in patients who underwent immediate breast reconstruction after mastectomy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-15-09.
Abstract P4-08-23: ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer
Authors: Chengheng Liao, Wentong Fang, Rachel Shi, Jeremy Simon, Travis Ptacek, Giada Zurlo, Youqiong Ye, Leng Han, Cheng Fan, Lei Bao, Christopher Llynard Ortiz, Hong-Rui Lin, Ujjawal Manocha, Weibo Luo, Yan Peng, William Y Kim, Lee-Wei Yang, Qing Zhang
Journal: Cancer Research (2023)

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive and highly lethal disease in women, while the oncogenic mechanisms which contribute to TNBC development, progression, and metastasis are poorly investigated and therefore warrant the critical need to identify novel oncogenic signalings and develop new therapeutic targets. Results: We show that Zinc Fingers and Homeoboxes 2 (ZHX2) is amplified or overexpressed in TNBC cell lines and patients. Functionally, depletion of ZHX2 inhibited TNBC cell growth and invasion in vitro, orthotopic tumor growth, and spontaneous lung metastasis in vivo. Mechanistically, ZHX2 bound with hypoxia-inducible factor (HIF) family members and positively regulated HIF1α protein level and activity in TNBC. Integrated ChIP-seq and gene expression profiling demonstrated that ZHX2 co-occupied with HIF1α on transcriptionally active promoters marked by H3K4me3 and H3K27ac, thereby promoting gene expression. Among the identified ZHX2 and HIF1α coregulated genes, overexpression of AP2B1, COX20, KDM3A, or PTGES3L could partially rescue TNBC cell growth defect by ZHX2 depletion, suggesting that these downstream targets contribute to the oncogenic role of ZHX2 in an accumulative fashion. Furthermore, multiple residues (R491, R581, and R674) on ZHX2 are important in regulating its phenotype, which correspond with their roles in controlling ZHX2 transcriptional activity in TNBC cells. These studies establish that ZHX2 activates oncogenic HIF1α signaling, therefore serving as a potential therapeutic target for TNBC. Conclusion: ZHX2 has been highlighted as one critical hypoxia-related factors regulator contributing to triple-negative breast cancer in this work, which has enriched the upstream regulatory network of HIF-1α signaling. Moreover, identification of key residuals determining biological function of ZHX2 provides novel approaches for treating TNBC via targeting the hypoxia pathway. Citation Format: Chengheng Liao, Wentong Fang, Rachel Shi, Jeremy Simon, Travis Ptacek, Giada Zurlo, Youqiong Ye, Leng Han, Cheng Fan, Lei Bao, Christopher Llynard Ortiz, Hong-Rui Lin, Ujjawal Manocha, Weibo Luo, Yan Peng, William Y Kim, Lee-Wei Yang, Qing Zhang. ZHX2 promotes HIF1α oncogenic signaling in triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-23.
Abstract P6-01-30: PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit
Authors: Christos Markopoulos, Mahi Sariyanni, Asimina Karamargiou, Zoi Antonopoulou, Nikolaos Tsoulos
Journal: Cancer Research (2023)

Abstract AIM: The majority of invasive lobular carcinomas (ILC) of the breast are luminal A tumors of good prognosis, having a low or intermediate OncotypeDX Recurrence Score (RS). They are usually treated with hormonal therapy only and some have doubted the relevance of the RS for patients with ILC. However, in a number of ILC cases a high RS can be found, indicating chemotherapy benefit. The aim of the present analysis was to explore in our database of lobular carcinomas analyzed with OncotypeDX, the percentage of tumors with a RS &amp;gt;25 and test the hypothesis if Progesterone Receptor (PgR) and/or Ki-67 expression could be an indicator to have patients evaluated with OncotypeDX. PATIENTS AND METHODS: Among 2.946 patients analyzed with Oncotype DX, we found 397 patients with pure lobular carcinomas (13.47%). Ki-67 expression was obtained from 315 patients and 13 of them (4%) had a high Ki-67 value of &amp;gt;30%. PgR expression was negative in 56 out of 397 patients (14%). We analyzed the possible relationship of RS values with PgR levels and Ki-67 expression. RESULTS: Overall, 94% of patients with ILC had a Recurrence Score ≤25 and only 6% (24/397) had a RS ≥26. There was a wide distribution of RS among patients with different values of PgR; however, there was a negative trend of Recurrence Score values and PgR expression levels. This trend was more obvious in the 56 patients with negative PgR expression. Although there were high RS values across all levels of Ki-67 expression, there was a trend towards high RS with higher Ki-67 expression; 5 out of 13 patients (38%) with ki-67 &amp;gt;30% had a RS ≥26. CONCLUSION: Our analysis shows that the majority of lobular carcinomas of the breast have a low OncotypeDX RS, suggesting that can be treated only with hormonal therapy. However, negative or low PgR levels and high Ki-67 expression might predict a high RS and thus chemotherapy benefit and those two parameters could be used as indicators for OncotypeDX evaluation of lobular carcinomas of the breast. Citation Format: Christos Markopoulos, Mahi Sariyanni, Asimina Karamargiou, Zoi Antonopoulou, Nikolaos Tsoulos. PgR levels and Ki67 expression of Lobular Carcinomas of the Breast might indicate OncotypeDX testing to evaluate Chemotherapy benefit [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-30.
Abstract P4-08-11: AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution
Authors: Amy Schade, Naiara Perurena, Marina Watanabe, Carrie L. Rodriguez, Patrick Loi, Natalie Pilla, Rachel A. Davis, Kaia Mattioli, Dongxi Xiang, Jason J. Zoeller, Zhe Li, Ana C. Garrido-Castro, Sara Tolaney, Karen Cichowski
Journal: Cancer Research (2023)

Abstract Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy, however responses are typically short-lived. Thus, there is an urgent need to develop more effective treatments. PI3K pathway components represent plausible therapeutic targets, as approximately 40% of TNBCs have PIK3CA/AKT1/PTEN alterations. However, unlike hormone receptor-positive tumors, it is still unclear if or how PI3K pathway inhibitors will be effective in triple-negative disease. Here we identify a promising AKT inhibitor-based therapeutic combination for TNBC. Specifically, we show that AKT inhibitors potently synergize with agents that suppress the histone methyltransferase, EZH2, and promote robust tumor regression in multiple TNBC models in vivo. AKT and EZH2 inhibitors exert these effects by first cooperatively driving basal-like TNBC cells into a more differentiated, luminal-like state, which cannot be effectively induced by either agent alone. More importantly, once differentiated, these agents kill TNBCs by hijacking signals that normally drive mammary gland involution. Together these findings identify a promising therapeutic strategy for this highly aggressive tumor type and illustrate how deregulated epigenetic enzymes can insulate tumors from oncogenic vulnerabilities. These studies also reveal how developmental tissue-specific cell death pathways may be co-opted for therapeutic benefit. Citation Format: Amy Schade, Naiara Perurena, Marina Watanabe, Carrie L. Rodriguez, Patrick Loi, Natalie Pilla, Rachel A. Davis, Kaia Mattioli, Dongxi Xiang, Jason J. Zoeller, Zhe Li, Ana C. Garrido-Castro, Sara Tolaney, Karen Cichowski. AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-11.
Abstract P6-05-53: “ANDEAN CARAVAN” &amp; “MAUCHIS PLATFORM”: 1st MOBILE CLINIC AND 1st ARTIFICIAL INTELLIGENCE PLATFORM AGAINST CANCER IN PERU
Authors: Mauricio León Rivera, Steffi Katheryne Gonzalez Bocanegra
Journal: Cancer Research (2023)

Abstract Science, Technology and Society have been related for many years with the goal of providing technological advances for the service of human development. Healthcare has not been immune to this influence and today there are numerous examples that promote the management of various diseases. Therefore, it is important to incorporate this technology into our daily lives, which will allow us to interact quickly and easily with various sectors of Peruvian society, regardless of their level of education or physical location. In this context, Technology and Innovation have become great allies in reinforcing health education and raising awareness of the importance of preventing and reducing the risks caused by cancer. By modifying some lifestyles for "healthy" ones, we would reduce the number of sick people. Knowing that in our country, 11 women die every day from breast and cervical cancer, totally preventable diseases that no one should die from; and that the government is completely overwhelmed in its preventive work, we decided to approach the mining industry. Together, we managed to create a "MOBILE CLINIC", an itinerant bus that will deliver medical care and perform oncological screening tests (Mammography, Ultrasound, Colposcopy and/or Laboratory Tests) to women from vulnerable populations in the communities that are within the area of ​​influence of formal mining in Peru. Similarly, during these meetings all residents will be taught about the use of our Artificial Intelligence platform "MAUCHIS", (www.mauchis.org). Mauchis is the first and only free Platform available 24 hours a day, 365 days a year in Latin America for the prevention of cancer accessible from Whatsapp (+51 1 994003265) and/or Facebook Messenger. This service is free, no payment will be accepted and no institution or company is promoted. Citation Format: Mauricio León Rivera, Steffi Katheryne Gonzalez Bocanegra. “ANDEAN CARAVAN” &amp; “MAUCHIS PLATFORM”: 1st MOBILE CLINIC AND 1st ARTIFICIAL INTELLIGENCE PLATFORM AGAINST CANCER IN PERU [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-53.
Abstract P6-03-08: Trained Artificial Intelligence (AI) for Predicting Treatment Termination Based on Patient Observations in Advanced Breast Cancer
Authors: Timo Schinköthe, Ronald Kates, Benedikt Sprecher, Silja Meyer, Christian Horst Tonk, Nadia Harbeck, Annette Schmidt
Journal: Cancer Research (2023)

Abstract Background: In various fields outside of medicine, AI-supported systems have been established that can predict an undesirable event. The purpose of such systems is to detect events earlier and, if necessary, to be able to prevent them. In medicine, it would be particularly interesting to be able to make such predictions based solely on patient observations. Methods: The usage from 323 patients with advanced breast cancer with a total of 78542 documentation days was used. In addition, the premature termination of use was defined as an undesirable event. The data was then processed and annotated. A deep-learning neural network (NN) classifier was trained on this dataset independently on all documented days to predict this target endpoint. The patient classifier score was computed by averaging over daily scores. Overall classifier accuracy and binary cross entropy loss were computed as performance indicators on training and test data sets (2:1 split). Results: After tuning the hyperparameters, the best-performing NN comprised three hidden layers, each with 88 neurons, using ReLU (linear ramp) activation, and an output layer using sigmoid activation. In the test collective, this model achieved a prediction accuracy of 87%. Discussion: The present application shows for the first time that treatment discontinuation can be predicted with a very high degree of accuracy using patient data alone. This opens up new possibilities in the early detection of possible therapy failures and can represent an essential auxiliary tool in medical care in the future. Citation Format: Timo Schinköthe, Ronald Kates, Benedikt Sprecher, Silja Meyer, Christian Horst Tonk, Nadia Harbeck, Annette Schmidt. Trained Artificial Intelligence (AI) for Predicting Treatment Termination Based on Patient Observations in Advanced Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-03-08.